Sorafenib, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N2-methylpyridine-2-carboxamide,
is a multikinase inhibitor. A method for its preparation is described in WO 00/42012.
Sorafenib tosylate, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N2-methylpyridine-2-carboxamide 4-methylbenzenesulfonate, is a pharmaceutically active agent which can be used for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma.
The preparation of different polymorphic forms of sorafenib tosylate, specifically polymorphic forms I, II, and III, is described in WO 2006/034797. In particular, WO 2006/034797 relates to the polymorphic form I, which is described as exhibiting superior stability in comparison to the other disclosed crystal forms. According to WO 2006/034797 this ensures that no undesired conversion to any other polymorph takes place as well as increased safety and quality of pharmaceutical preparations comprising polymorph I.
WO 2006/094626 relates to pharmaceutical compositions containing sorafenib. Among others, polymorphs in general, solvates, hydrates, and pharmaceutically acceptable salts of sorafenib are mentioned. As to the polymorphs, only the polymorphic form I is specifically mentioned.
WO 2009/092070 describes a processes for the preparation of the polymorphic forms I, II, and III of sorafenib tosylate, and further describes the preparation of a methanol solvate, an ethanol solvate, and a hemi-tosylate. Pharmaceutical compositions containing said compounds are only generally mentioned, and WO 2009/092070 is silent on specific pharmaceutical compositions, and no example is directed to a pharmaceutical composition.
Sorafenib tosylate is currently marketed as a coated tablet for immediate release under the trade name of Nexavar®, wherein the tablets contain the sorafenib tosylate having polymorphic form I. The tablets are packaged in expensive aluminum blisters, which are practically impermeable to water.
Additionally, in case the marketed tablets are to be dispersed in water prior to their use which becomes necessary if the respective patient in need of sorafenib tosylate struggles with swallowing problems or if the composition is to be fed to the patient via a tube, the disintegration of a tablet takes about 6 minutes. This very slow disintegration behaviour is another major drawback of the marketed tablets.
Further, the marketed tablets contain sodium lauryl sulfate which is usually used as surfactant or wetting agent. However, such a surfactant may impair both the taste and the gastric tolerability of the formulation, in particular in case the tablets have to be dispersed in water prior to their use and no taste masking is possible.
Therefore, there is a need for pharmaceutical compositions, in particular oral solid dosage forms, comprising sorafenib tosylate as active agent which allow the use of less expensive packaging materials.
Further, there is a need for pharmaceutical compositions, in particular oral solid dosage forms, comprising sorafenib tosylate as active agent which have an increased disintegration rate.
Yet further, there is need for pharmaceutical compositions, in particular oral solid dosage forms, which overcome the disadvantages of compositions containing critical surfactants such as sodium lauryl sulfate.